Modeling the Differentiation of Embryonic Limb Chondroprogenitors by Cell Death and Cell Senescence in High Density Micromass Cultures and Their Regulation by FGF Signaling
Considering the importance of programmed cell death in the formation of the skeleton during embryonic development, the aim of the present study was to analyze whether regulated cell degeneration also accompanies the differentiation of embryonic limb skeletal progenitors in high-density tridimensiona...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-12-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/12/1/175 |
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| author | Cristina Duarte-Olivenza Juan M. Hurle Juan A. Montero Carlos I. Lorda-Diez |
| author_facet | Cristina Duarte-Olivenza Juan M. Hurle Juan A. Montero Carlos I. Lorda-Diez |
| author_sort | Cristina Duarte-Olivenza |
| collection | DOAJ |
| description | Considering the importance of programmed cell death in the formation of the skeleton during embryonic development, the aim of the present study was to analyze whether regulated cell degeneration also accompanies the differentiation of embryonic limb skeletal progenitors in high-density tridimensional cultures (micromass cultures). Our results show that the formation of primary cartilage nodules in the micromass culture assay involves a patterned process of cell death and cell senescence, complementary to the pattern of chondrogenesis. As occurs in vivo, the degenerative events were preceded by DNA damage detectable by γH2AX immunolabeling and proceeded via apoptosis and cell senescence. Combined treatments of the cultures with growth factors active during limb skeletogenesis, including FGF, BMP, and WNT revealed that FGF signaling modulates the response of progenitors to signaling pathways implicated in cell death. Transcriptional changes induced by FGF treatments suggested that this function is mediated by the positive regulation of the genetic machinery responsible for apoptosis and cell senescence together with hypomethylation of the <i>Sox9</i> gene promoter. We propose that FGF signaling exerts a primordial function in the embryonic limb conferring chondroprogenitors with their biological properties. |
| first_indexed | 2024-03-11T10:05:18Z |
| format | Article |
| id | doaj.art-d703a918595844ac9add0fd3beced4b7 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-11T10:05:18Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-d703a918595844ac9add0fd3beced4b72023-11-16T15:07:06ZengMDPI AGCells2073-44092022-12-0112117510.3390/cells12010175Modeling the Differentiation of Embryonic Limb Chondroprogenitors by Cell Death and Cell Senescence in High Density Micromass Cultures and Their Regulation by FGF SignalingCristina Duarte-Olivenza0Juan M. Hurle1Juan A. Montero2Carlos I. Lorda-Diez3Departamento de Anatomía y Biología Celular and IDIVAL, Universidad de Cantabria, 39011 Santander, SpainDepartamento de Anatomía y Biología Celular and IDIVAL, Universidad de Cantabria, 39011 Santander, SpainDepartamento de Anatomía y Biología Celular and IDIVAL, Universidad de Cantabria, 39011 Santander, SpainDepartamento de Anatomía y Biología Celular and IDIVAL, Universidad de Cantabria, 39011 Santander, SpainConsidering the importance of programmed cell death in the formation of the skeleton during embryonic development, the aim of the present study was to analyze whether regulated cell degeneration also accompanies the differentiation of embryonic limb skeletal progenitors in high-density tridimensional cultures (micromass cultures). Our results show that the formation of primary cartilage nodules in the micromass culture assay involves a patterned process of cell death and cell senescence, complementary to the pattern of chondrogenesis. As occurs in vivo, the degenerative events were preceded by DNA damage detectable by γH2AX immunolabeling and proceeded via apoptosis and cell senescence. Combined treatments of the cultures with growth factors active during limb skeletogenesis, including FGF, BMP, and WNT revealed that FGF signaling modulates the response of progenitors to signaling pathways implicated in cell death. Transcriptional changes induced by FGF treatments suggested that this function is mediated by the positive regulation of the genetic machinery responsible for apoptosis and cell senescence together with hypomethylation of the <i>Sox9</i> gene promoter. We propose that FGF signaling exerts a primordial function in the embryonic limb conferring chondroprogenitors with their biological properties.https://www.mdpi.com/2073-4409/12/1/175apoptosiscell senescencechondrogenesis |
| spellingShingle | Cristina Duarte-Olivenza Juan M. Hurle Juan A. Montero Carlos I. Lorda-Diez Modeling the Differentiation of Embryonic Limb Chondroprogenitors by Cell Death and Cell Senescence in High Density Micromass Cultures and Their Regulation by FGF Signaling Cells apoptosis cell senescence chondrogenesis |
| title | Modeling the Differentiation of Embryonic Limb Chondroprogenitors by Cell Death and Cell Senescence in High Density Micromass Cultures and Their Regulation by FGF Signaling |
| title_full | Modeling the Differentiation of Embryonic Limb Chondroprogenitors by Cell Death and Cell Senescence in High Density Micromass Cultures and Their Regulation by FGF Signaling |
| title_fullStr | Modeling the Differentiation of Embryonic Limb Chondroprogenitors by Cell Death and Cell Senescence in High Density Micromass Cultures and Their Regulation by FGF Signaling |
| title_full_unstemmed | Modeling the Differentiation of Embryonic Limb Chondroprogenitors by Cell Death and Cell Senescence in High Density Micromass Cultures and Their Regulation by FGF Signaling |
| title_short | Modeling the Differentiation of Embryonic Limb Chondroprogenitors by Cell Death and Cell Senescence in High Density Micromass Cultures and Their Regulation by FGF Signaling |
| title_sort | modeling the differentiation of embryonic limb chondroprogenitors by cell death and cell senescence in high density micromass cultures and their regulation by fgf signaling |
| topic | apoptosis cell senescence chondrogenesis |
| url | https://www.mdpi.com/2073-4409/12/1/175 |
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